Elucidation of the anti-head and neck squamous cell carcinoma mechanism of Phellinus baumii polyphenol based on network pharmacology and experimental verification

doi:10.11958/20250580

Abstract

Abstract:

Objective To investigate the effects of Phellinus baumii polyphenol (PBP) on head and neck squamous cell carcinoma (HNSCC) and analyze the potential mechanism based on network pharmacology and in vitro experiments. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), DrugBank, GeneCards, Comparative Toxicogenomics Database (CTD) and Online Mendelian Inheritance in Man (OMIM) database were used to screen the active components of PBP and potential targets of PBP on HNSCC. The potential target interaction network was constructed using String database, and the core targets were screened by two-step topology analysis. Enrichment analysis of potential targets was performed using the DAVID database. Human HNSCC cell lines SCC-15 and SCC-25 were cultured in vitro using PBP intervention of 0, 25, 50 mg/L, respectively. The cell proliferation and colony formation ability were detected by cell counting reagent (CCK-8) and colony formation assay. Western blot assay was used to detect the expression of PBP core target protein in 2 cell lines. Results A total of 280 targets were identified for 17 active components of PBP, 264 of which were HNSCC-related genes. Two-step topology analysis showed that hypoxia inducible factor 1 subunit alpha (HIF1A), tumor protein p53 (TP53), AKT serine/threonine kinase 1 (AKT1), signal transducer and activator of transcription 3 (STAT3), cyclin A2 (CCNA2) and JUN proto-oncogene (JUN) were the core targets. The enrichment results suggested that PBP may play a role in HNSCC through various pathways. In vitro experiment results showed that with the increase of PBP intervention concentration, the proliferation ability and colony formation ability of SCC-15 and SCC-25 cells were significantly decreased (P<0.05), while the protein expression levels of STAT3, AKT1 and CCNA2 were decreased (P<0.05). Conclusion PBP can inhibit the progression of HNSCC by multi-target and multi-pathway.

Key words: head and neck neoplasms, fungi, gene regulatory networks, cell proliferation, P. baumii polyphenol

CLC Number:

R739.81

Figures/Tables 8

Fig.1 Potential target analysis of PBP on HNSCC

Fig.2 Two-step topology analysis of the core targets of PBP in HNSCC

Fig.3 KEGG enrichment analysis of potential targets of PBP on HNSCC

Fig.4 Proliferation curves of SCC-15 and SCC-25 cells after intervention with different concentrations of PBP

Fig. 5 Effects of different concentrations of PBP on colony formation capacity of SCC-15 and SCC-25 cells

Tab.1 Comparison of the number of cell colonies between three groups

组别	SCC-15集落数/个	SCC-25集落数/个
0 mg/L PBP组	115.67±6.03	63.33±7.63
25 mg/L PBP组	90.33±9.00^a	37.67±2.52^a
50 mg/L PBP组	55.67±4.04^ab	22.33±2.52^ab
F	61.393^＊＊	54.399^＊＊

Fig. 6 Effect of PBP on STAT3, AKT1 and CCNA2 protein expression in SCC-15 and SCC-25 cells

Tab.2 Comparison of cell protein levels between two groups

组别	SCC-15
组别	STAT3	AKT1	CCNA2
0 mg/L PBP组	1.00±0.02	1.00±0.04	1.00±0.01
50 mg/L PBP组	0.55±0.08	0.69±0.05	0.38±0.06
t	8.873^＊＊	7.783^＊＊	16.231^＊＊
组别	SCC-25
组别	STAT3	AKT1	CCNA2
0 mg/L PBP组	1.00±0.04	1.00±0.01	1.00±0.01
50 mg/L PBP组	0.77±0.01	0.39±0.06	0.52±0.05
t	8.304^＊＊	15.550^＊＊	13.705^＊＊

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